Nose-to-brain administration of drugs

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Nose-to-brain administration of drugs

Postby thinkingoutloud86 » Mon Feb 04, 2008 12:19 am

Found this article...although it is about Alzheimer's disease, what stood out was the concept of administering meds via the nose and how it apparently circumvents the blood-brain barrier...has anyone heard of using this approach for a MS med?

http://www.twincities.com/allheadlines/ci_8160098

Nose to brain is a promising path in Alzheimer's fight
Regions Hospital researcher's nasal-spray discoveries get renewed attention
BY JEREMY OLSON
Pioneer Press
Article Last Updated: 02/03/2008 11:58:49 PM CST

A nasal spray that could treat Alzheimer's disease - a dream more than two decades in the making for one Twin Cities researcher - is getting more attention these days.

Several studies are using the nose-to-brain method of delivering drugs that was invented in the late 1980s and patented by William Frey II, director of an Alzheimer's research center at Regions Hospital in St. Paul. Last month, researchers in Washington state reported using intranasal insulin to improve memory and attention for patients with early-stage Alzheimer's.

The study is the latest support for Frey's basic discovery - that drugs targeted at nerve endings in the upper portion of the nose can rush to the brain and bypass the protective blood-brain barrier.

Whether it's the secret to beating Alzheimer's is unclear. Doctors and scientists have proposed dietary changes, vitamin supplements, stem cell therapies and vaccines to prevent or treat the now-incurable disease. Frey's work at least gives hope against a disease that is the seventh-leading cause of death in the U.S.

The nose-to-brain discovery was so simple that Frey spent years convincing officials at the U.S. Patent Office that it was a useful method of drug delivery. Then he spent several more years convincing them that it was an actual discovery and not just a feature of anatomy.

"Some people would say it's as simple as the nose on your face - that everybody already knew that," Frey said. "But the truth of the matter
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is, no, nobody knew it."

AVOIDING THE BLOCKADE

Most nasal sprays are directed to the lower part of the nose so medication can quickly enter the bloodstream. Drugs to treat neurological conditions don't work through this route, though, because of the protective blood-brain barrier.

While this blockade of cells and blood vessels protects the brain and spinal chord from harmful organisms, it also keeps out most drugs and has stymied otherwise promising therapies.

Avoiding this barrier is what makes intranasal delivery "a potentially powerful therapeutic tool," according to the Washington research group. Its study was small, with 24 patients receiving daily insulin or a placebo, but the results, published in the journal Neurology, were persuasive.

Patients taking intranasal insulin were mentally sharper, and their blood sugar levels remained healthy.

Several companies have made nasal spray devices that can target this nose route to the brain, but it's unclear if any drugs will take advantage of it.

Frey recently gained federal funding to study the intranasal delivery of deferoximine, a generic drug that removes toxic amounts of iron and other metals from the body. One theory about Alzheimer's is that excess metals in the brain cause oxidation and damage to the neurons - the brain's thinking cells.

Canadian company Allon Therapeutics is in the second phase of U.S. clinical trials with an experimental drug that may support the growth and repair of brain cells. The intranasal drug is being evaluated as a treatment for Alzheimer's and schizophrenia.

Insulin might hold the most immediate promise, given that insulin injections have been used safely for years to treat diabetes. There is building research, including the Washington study, that insulin plays a crucial role in Alzheimer's and other diseases that erode memory and thinking skills.

"The brain needs insulin to help brain cells take up blood sugar," Frey said. "It gives them the energy they need so you can think and remember."

COMPANY NOT INTERESTED

A drug company's disinterest could slow the development of this potential therapy. Chiron, a subsidiary of Novartis, holds patents for the intranasal delivery of insulin and drugs that mimic insulin. (Both patents were sold to the drug company by HealthPartners - the health system that owns Regions - and still list Frey as the inventor.)

When asked if Novartis is developing the ideas in these patents, a spokesman replied, "We're not."

It's disappointing to Frey and other believers. The idea offers limited financial returns for Novartis, because it doesn't involve the development of a new drug the company could provide exclusively to the market.

Still, it's an untapped market. Few therapies exist for the estimated 5.1 million Americans with Alzheimer's. A primary drug is Aricept, which slows the degeneration caused by Alzheimer's but doesn't halt or reverse the disease.

Drug companies are studying other Alzheimer's treatments, and research institutions are finding more apparent targets in the brain.

Researchers at the University of Minnesota, for example, have discovered a unique cluster of proteins in mice that is connected to memory loss. They suspect drugs could prevent this cluster from forming in human brains, which could prevent or treat Alzheimer's.

Frey doesn't know whether his research could end up targeting symptoms of Alzheimer's or whether it could cure the disease altogether. Drug companies are interested in his findings, and he is meeting with them in the coming weeks.

He spent last week in California at a lab that will help conduct the studies with deferoximine, the iron-reducing drug. The goal is to study in animals whether intranasal use of that drug is safe.

If safety is proven, Frey said, he could start to pursue human clinical trials by the end of the year.
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Re: Nose-to-brain administration of drugs

Postby NHE » Mon Feb 04, 2008 3:38 am

thinkingoutloud86 wrote:what stood out was the concept of administering meds via the nose and how it apparently circumvents the blood-brain barrier...has anyone heard of using this approach for a MS med?

I don't know if this is "nose-to-brain" per se, but a company called Apitope is currently developing a vaccine based on peptides from myelin basic protein which are delivered intranasally.

The vaccine's name is ATX-MS-1467.

NHE
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Postby Lyon » Mon Feb 04, 2008 7:34 am

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Postby chrishasms » Mon Feb 04, 2008 7:54 am

What amazes me is it crossing the BBB that easily through the nose.

Can you imagine if it was a genetic defect in our immune system's and simply inhaling deeply at the *wrong* time in life and *WHAMO* you got MS.

Can you imagine if they researched the idea of Mono, Flu, Bronchitis, or Herpes Outbreak even, and the ability to inhale MS.

Now, what the hell is inhaled to get MS at that time?

I just find that info FASCINATING!!!

The last thing I needed was more stuff to ponder and now here I am pondering. Ponderous Man, Real Ponderous!
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Postby Loobie » Mon Feb 04, 2008 8:13 am

I think it will require a significant amount of pondification.
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Postby dignan » Mon Feb 04, 2008 8:57 am

It has been around for a little while. A company called Nastech trialed an inhaled interferon formulation, but it fizzled out. Right now, in the preclinical section of the pipeline list is this:

63. Syntonix Transceptor/SynFusion (inhaled interferon-beta:Fc) (Syntonix/Serono)
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Postby Lyon » Mon Feb 04, 2008 2:00 pm

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Postby thinkingoutloud86 » Mon Feb 04, 2008 2:22 pm

Chris...didn't mean to set off all of that pondering :)...wasn't really trying to suggest that MS may be the result of an airborne pathogen...I'm not about to wear that nose plug at the grocery store and I hope that you have held off as well...

To everyone else...thanks for the info...its too bad that the interferon didn't work out at first....maybe in the future

TOL
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Postby Terry » Mon Feb 04, 2008 5:00 pm

Chris,
There are pathogens that live in the nose, you know. You have to wonder. Another thing I've been wondering is why most MSers first symptom is in the optic nerve. Wouldn't that be closer to the nose?
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Postby Terry » Mon Feb 04, 2008 5:47 pm

found this

Infection and tumors in the sphenoid sinuses can progress into the optic nerve, cavernous sinus, carotid artery, and sella turcica.
[/quote]
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Postby cheerleader » Thu Feb 07, 2008 11:04 am

WOW...
Thanks for this, Thinking!
Hubby always has red nose, sneezing, sinusitis, nasal allergies.
Could nasal passage be implicated in breaking of blood brain barrier with those nasty molecular mimicking bacteria? Inquiring minds want to know.

Found a product to try out on the nasal passageway...
antifungal, antibacterial -"SinoFresh"
Maybe it can give him a minty fresh brain, too :)

http://www.natlallergy.com/product.asp? ... 1202407082

best,
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby Terry » Thu Feb 07, 2008 4:09 pm

Thanks for posting on this thread, Cheerleader. My post was just hanging out there- flapping in the wind. I was thinking, okay, these people must think I'm crazy, not even a reply! But it does kind of make sense. (No, not the crazy thing--- the nose/ optic nerve thing)
I'm glad to see your here, Cheerleader. I know you were overwhelmed for a while. I got that way a liitle while back and took a rest from reading anything MS related. I waited about 2.2 seconds and went at it again. I even told my doc that I'm sure I need to quit reading and thinking about it, then I told him that I'm sure I won't!!
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Postby Jim_P » Thu Feb 07, 2008 4:51 pm

I was actually considering doing lines of N-Acetylglucosamine. The stuff I have is in powder form after all. :P
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Quotation source

Postby lyndacarol » Thu Feb 07, 2008 6:26 pm

Terry, I am very interested in your line of thought. I had sent you a private message, trying to get more info (guess you don't check for your PMs); so I'll ask again openly here: "What is the source for your quote?"

I think you are definitely on to something here!
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Postby Terry » Thu Feb 07, 2008 6:37 pm

I had to search it again, but here it is.

http://www.aaaai.org/members/committee_info/sinusitis_practice_parameters.stm

I hope it links.
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